The proposed interdisciplinary study allows the candidateto further develop his knowledge of MR physics and expertise in imaging studies of adrenomyeloneuropathy(AMN), a form of adrenoleukodystrophy(AID), while providing rigorous exposureto the clinical and biological side of this research. The goal is to increase the candidate's expertise in multiple areas necessary to his proposed research project and future career development. These areas include genetics of peroxisomaldisorders, lipid metabolism, and spatialaspects of nuclear magnetic resonancespectroscopy. The proposal builds nicely on the candidate's priorexperience with Dr. Moser at Johns Hopkins and extends his studies to the animal model. The candidate is in a world- renown environment for both MR imaging and neuroscience. This award will provide the guidance and tools necessary for him to become a successful, independent researcher. The 5 year researchtraining program consists of 1) coursework&mentoring relationships on the science of high-field magnetic resonance that the candidate is currently lacking 2) a 2 year rigorous training in animal imaging 3) collaborative translational studies with experts in the field of lipid metabolism and peroxisomal disorders. The research portion of this application will allow him to examine the histopathological and biochemical correlate of advanced MR techniques in the mouse model of ALD. This has never been done before and likely to reveal insight into the fundamental dynamics of demyelination. Further, the proposalencompasses application of novel therapeutics to normalize lipid metabolism and stabilize myelin membrane integrity. Hypotheses include: 1) in the animal model of ALD, measures of diffusion tensor imaging can assess the density of white matter tracts in the mouse and measures of single voxel proton MR spectroscopy reflect changes in lipid composition of the brain. 2) in ALD patients, metabolic changes seen on proton MR spectroscopic imaging herald lesion development on conventional MRI. Our results will yield a noninvasive means of gauging the effects of experimental and therapeutic manipulations of lipid chemistry upon specific neuroanatomic structures. Ultimately, insights gained in these studies of ALD/AMNmay prove beneficial to other neurodegenerative diseases, such as amyotrophic lateral sclerosis or Parkinson's and Alzheimer's diseases.